tbuckley/cabot-search huggingface dataset:
OP0105 miRNOME PROFILE IN PATIENTS WITH AXIAL SPONDYLOARTHRITIS
Authors: A. Pekacova, J. Baloun, K. Bubova, M. Gregová, S. Forejtova, J. Horinkova, M. Husakova, M. Tomčík, J. Gatterova, J. Vencovský, K. Pavelka, L. Šenolt
Journal: Annals of the Rheumatic Diseases (2022)

Background microRNAs (miRNAs) are small non-coding RNAs regulating up to 60 % of human mRNAs, including genes related to axial spondyloarthritis (axSpA) (1). Objectives This study aims to profile miRNome and to identify candidate miRNAs determining disease severity in patietns with non-radiographic (nr) and radiographic (r) axSpA. Methods The miRNome profiling experiment included peripheral blood mononuclear cells (PBMCs) of 96 subjects (38 patients with nr-axSpA, 38 patients with r-axSpA and 20 healthy controls). Firstly, massive parallel sequencing on NextSeq 500 (MPS, Illumina) was performed for miRNA screening. Selected candidate miRNAs were further validated using the qRT-PCR system (SmartChip) on the validation cohort of 141 subjects (47 patients with nr-axSpA, 44 patients with r-axSpA and 50 healthy controls). We employed the DESeq2 algorithm and generalized linear modelling with a negative binomial assumption (GLM-NB) to evaluate the association of candidate miRNAs to axSpA subtype and clinical disease activity (ASDAS and CRP). Results MPS revealed 432 unique miRNAs in all samples. We identified 13 differently expressed miRNAs in axSpA patients compared to healthy controls, and 14 differently expressed miRNAs in axSpA patients with high to very high ASDAS compared to patients with inactive disease. Data from validation cohort revealed that the expression level of miR-4286 was higher in patients with very high disease activity compared to patients with inactive disease. Simultaneously, miR-4286 positively correlated with ASDAS. miR-4286 has been recently associated with osteogenesis and angiogenesis (2). None of the validated miRNAs was associated with the levels of CRP. Conclusion In this study, we identified that miR-4286 is related to disease activity and could play a role in the pathogenesis of axSpA. References [1]Prajzlerová K, Grobelná K, Hušáková M, et al. Association between circulating miRNAs and spinal involvement in patients with axial spondyloarthritis. PLoS One. 2017 Sep 22;12(9):e0185323. [2]Yu H, Wang K, Liu P, et al. miR-4286 functions in osteogenesis and angiogenesis via targeting histone deacetylase 3 and alleviates alcohol-induced bone loss in mice. Cell Prolif. 2021 Jun;54(6):e13054. Acknowledgements Supported by MHCR No. 023728, BBMRI-CZ LM2018125 and SVV 260 523. Disclosure of Interests None declared
OP0245 ASSOCIATION OF BARIATRIC SURGERY WITH THE RISK OF FRACTURE IN PATIENTS WITH OBESITY: A META-ANALYSIS OF REAL-WORLD EVIDENCE
Authors: S. Hussain, J. Klugarova, M. Klugar
Journal: Annals of the Rheumatic Diseases (2022)

Background Evidence from published epidemiological studies found inconsistent evidence on the association of bariatric surgery with fracture risk. Objectives To evaluate the impact of bariatric surgery on fracture risk. Methods Electronic databases PubMed, and Embase were searched for studies assessing the association between bariatric surgery and fracture risk by two independent investigators. The study search period was from inception to September 2021. Study selection, data extraction, and risk of bias were assessed by investigators independently. Newcastle-Ottawa Scale (NOS) was used to assess the risk of bias. The primary outcome was to compute the pooled fracture risk in patients with obesity who underwent bariatric surgery. Secondary outcomes include fracture risk based on follow-up duration and sites of fracture (hip, upper limb). Certainty of findings was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) criteria. Results This meta-analysis was based on seven studies with a total of 156233 patients with a mean age of 41.65 ± 10.63 years. Included studies were of low risk of bias. A significantly increased risk of any fracture was found in the bariatric surgery group as compared to the non-surgical group with a pooled relative risk (RR) of 1.34 (95% CI: 1.05 – 1.70), p = 0.02 (Figure 1). Figure 1. Forest plot showing high fracture risk in the bariatric surgery group Subgroup analysis based on follow-up duration also revealed a significantly higher fracture risk with a RR of 1.75 (95% CI: 1.34 – 2.30), p = &lt;0.0001 for studies with a follow-up period of &gt;5 years. Likewise, analysis based on fracture sites revealed a significantly higher risk of hip fracture RR 1.34 (95% CI: 1.03 – 1.75), p =0.03 (Figure 2). Evidence was of low certainty as per the GRADE rating system. Figure 2. Forest plot showing high hip fracture risk in the bariatric surgery group Conclusion The current study found that bariatric surgery was associated with increased fracture risk. Clinicians should also evaluate the bone health profiling of the patients before the surgery. References [1]Khalid SI, et al. Association of bariatric surgery with risk of fracture in patients with severe obesity. JAMA network open. 2020;3(6):e207419. Disclosure of Interests None declared
OP0242 ASSOCIATION BETWEEN EXPOSURE TO FINE PARTICULATE MATTER AND OSTEOPOROSIS: A POPULATION-BASED COHORT STUDY
Authors: G. Adami, C. Benini, A. Fassio, E. Bertoldo, O. Viapiana, D. Gatti, M. Rossini
Journal: Annals of the Rheumatic Diseases (2022)

Background Environmental air pollution has been associated with disruption of bone health at a molecular level. Particulate matter (PM) exposure can simultaneously stimulate bone resorption and halt bone formation. Objectives The primary aim of the present study is to describe the association between long-term exposure to PM and osteoporosis in a large cohort of women at high risk of fracture. Methods Clinical, demographic and densitometric data were extracted from the DeFRAcalc79 dataset, which gathers data on women at risk for osteoporosis. Data on the monitoring of PM10 and PM2.5 concentrations were retrieved from the Italian institute of environment protection and research (Istituto Superiore per la Protezione e la Ricerca Ambientale, ISPRA). Every study subject was linked to a PM exposure value, which resulted from the average concentration of urban, rural and near-traffic stations of the subject residency (ZIP code centroids 25 km) from January 2013 to December 2019. Generalized linear models with robust estimators were employed to determine the relationship between BMD and PM long-term exposure. We sequentially adjusted for confounders. Model 1 included age, body mass index (BMI), presence of prevalent fragility fractures, family history of vertebral or hip fractures, and menopause. Model 2 was further adjusted for glucocorticoid treatment and comorbidities. Model 3 (main model) added to model 2 the macro-area of residency (stratified as a categorical variable: northern Italy, central Italy and southern Italy). Results 59,950 women from 110 Italian provinces were included in the study. PM 2,5 exposure was negatively associated with T-score levels at the femoral neck (β -0.005, 95 CI -0.007 to -0.003) and lumbar spine (β -0.003, 95% CI -0.006 to -0.001). Chronic exposure to PM2.5 above 25 μg/m 3 was associated with a 16% higher risk of having osteoporotic T-score at any site (aOR 1.161, 95% CI 1.105 to 1.220), exposure to PM10 above 30 μg/m 3 was associated with a 15% higher risk of having osteoporotic T-score at any site (aOR 1.148, 95% CI 1.098 to 1.200). Conclusion Long-term exposure to air pollution was associated with higher risk of osteoporosis. Femoral neck site seemed to be more susceptible to the detrimental effect of PM exposure than lumbar spine site. Disclosure of Interests Giovanni Adami Shareholder of: Galapagos, Theramex, Camilla Benini: None declared, Angelo Fassio: None declared, Eugenia Bertoldo: None declared, Ombretta Viapiana: None declared, Davide Gatti: None declared, Maurizio Rossini Shareholder of: Abbvie, Amgen, Bms, Eli Lilly, Galapagos, Novartis, Pfizer, Sandoz, Theramex, Ucb.
OP0040-PARE THE WEBINAR SERIES FOR THE PATIENTS “PREGNANCY AFTER DIAGNOSING ANKYLOSIS SPONDYLITIS”
Authors: O. Krichevskaya, T. Dubinina, N. Klimenchenko, N. Shatalova
Journal: Annals of the Rheumatic Diseases (2022)

Background Having been diagnosed with ankylosis spondylitis (AS), 68,2% of females in Russia reconsider their plans for pregnancy, with 13% giving up motherhood altogether out of fear for their own and their child’s potential health problems. However, most females allow pregnancy while experiencing emotional discomfort and anxiety 1 . Objectives To shed more light on the mutual influence of AS and pregnancy, AS pregnancy outcomes, clinical course of AS as well as medication options during AS and lactation. Methods From 03/2021 to 12/2021 an on-line series of eight webinars was conducted together with the patients’ Russian ankylosing spondylitis association. Each webinar included lectures of one or two rheumatologists and an obstetrician; furthermore, the series included the presentations of a physical therapy instructor (with the demonstration of exercises) and of a breast-feeding specialist. After the lecture each speaker answered the audience’s questions. Topics of rheumatologists’ lectures were “AS and pregnancy: problem introduction”, “What do we know about AS genetics”, “Features of pregnancy planning” (included therapy issues for men with AS who are planning to father a child), “Rheumatologist prenatal and postnatal care” (included the analysis of AS clinical manifestations such as potential changes in back pain type),“Contemporary approaches to AS pregnancy treatment”. A brochure for the patients with the main provisions of the lectures had been developed in support of the series. Results Webinars scored 703±192 views (by 29.01.2022). According to the questionnaire survey of the audience, 43,8% first knew that it was necessary to plan AS pregnancy minimum 3-6 months before conception; 25% – that conception is optimal during remission or low AS activity; 31,3% – that medical therapy can be continued during pregnancy; 18,8% – that it is necessary to inform the obstetrician about AS diagnosis and therapy received. 80% of the participants are fully satisfied with the information provided by the web series; 13,3% – reported not to had received enough information. Conclusion The interest in webinars shows that the choice of the form and the information provided was successful. The content of the series can be used to develop FAQ-section on the patient’s website “Ankylosing Spondylitis Association». In 2022, lectures will continue taking into account patients’ feedback. References [1]Z.Gandaloeva, O.Krichevskaya, T.Dubinina. Plans for motherhood are changed after diagnosing ankylosis spondylitis (AS). AS female patients’ attitude to the use of as medications during pregnancy planning and conception. Ann Rheum Dis, 2019; 78 (2), A1241DOI:10.1136/annrheumdis-2019-eular.3958 Disclosure of Interests None declared.
Covid-19 in Philadelphia-negative myeloproliferative neoplasms: a GIMEMA survey on incidence, clinical management and vaccine
Authors: M. Breccia, A. Piciocchi, M. Messina, S. Soddu, V. De Stefano, M. Bellini, A. Iurlo, B. Martino, S. Siragusa, F. Albano, B. Mora, P. Fazi, M. Vignetti, P. Guglielmelli, F. Palandri
Journal: Leukemia (2022)
Awards, Appointments, Announcements
Journal: JNCI Journal of the National Cancer Institute (1993)

Journal Article Awards, Appointments, Announcements Get access JNCI: Journal of the National Cancer Institute, Volume 85, Issue 18, 15 September 1993, Pages 1458–1459, https://doi.org/10.1093/jnci/85.18.1458 Published: 15 September 1993
Pediatric Manpower in United States and Its Implications
Journal: JAMA (1963)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Endoscopic Ultrasonography
Authors: M J Bruno
Journal: Endoscopy (2003)

A survey on physician attitudes regarding endoscopic ultrasonography (EUS) and its availability was sent to gastroenterologists and surgeons involved in the care of patients with gastrointestinal tract cancers in three separate urban regions of the USA [1]. Preliminary results from 10 % of a total of 2211 surveys were reported. Only 5 % of respondents performed EUS themselves. Thirty-eight percent currently had no readily available access to diagnostic or interventional EUS. Thirty-two percent had never utilized EUS in the staging of esophageal, rectal, or pancreatic cancers. Inadequate training opportunities (52 %) and the high equipment costs (39 %) were cited as the greatest barriers to learning and performing EUS.
Safety and efficacy of pralsetinib in RET fusion–positive non-small-cell lung cancer including as first-line therapy: update from the ARROW trial
Authors: F. Griesinger, G. Curigliano, M. Thomas, V. Subbiah, C.S. Baik, D.S.W. Tan, D.H. Lee, D. Misch, E. Garralda, D.-W. Kim, A.J. van der Wekken, J.F. Gainor, L. Paz-Ares, S.V. Liu, G.P. Kalemkerian, Y. Houvras, D.W. Bowles, A.S. Mansfield, J.J. Lin, V. Smoljanovic, A. Rahman, S. Kong, A. Zalutskaya, M. Louie-Gao, A.L. Boral, J. Mazières
Journal: Annals of Oncology (2022)

RET fusions are present in 1%-2% of non-small-cell lung cancer (NSCLC). Pralsetinib, a highly potent, oral, central nervous system-penetrant, selective RET inhibitor, previously demonstrated clinical activity in patients with RET fusion-positive NSCLC in the phase I/II ARROW study, including among treatment-naive patients. We report an updated analysis from the ARROW study.ARROW is a multi-cohort, open-label, phase I/II study. Eligible patients were ≥18 years of age with locally advanced or metastatic solid tumours and an Eastern Cooperative Oncology Group performance status of 0-2 (later 0-1). Patients initiated pralsetinib at the recommended phase II dose of 400 mg once daily until disease progression, intolerance, consent withdrawal, or investigator's decision. The co-primary endpoints (phase II) were overall response rate (ORR) by blinded independent central review and safety.Between 17 March 2017 and 6 November 2020 (data cut-off), 281 patients with RET fusion-positive NSCLC were enrolled. The ORR was 72% [54/75; 95% confidence interval (CI) 60% to 82%] for treatment-naive patients and 59% (80/136; 95% CI 50% to 67%) for patients with prior platinum-based chemotherapy (enrolment cut-off for efficacy analysis: 22 May 2020); median duration of response was not reached for treatment-naive patients and 22.3 months for prior platinum-based chemotherapy patients. Tumour shrinkage was observed in all treatment-naive patients and in 97% of patients with prior platinum-based chemotherapy; median progression-free survival was 13.0 and 16.5 months, respectively. In patients with measurable intracranial metastases, the intracranial response rate was 70% (7/10; 95% CI 35% to 93%); all had received prior systemic treatment. In treatment-naive patients with RET fusion-positive NSCLC who initiated pralsetinib by the data cut-off (n = 116), the most common grade 3-4 treatment-related adverse events (TRAEs) were neutropenia (18%), hypertension (10%), increased blood creatine phosphokinase (9%), and lymphopenia (9%). Overall, 7% (20/281) discontinued due to TRAEs.Pralsetinib treatment produced robust efficacy and was generally well tolerated in treatment-naive patients with advanced RET fusion-positive NSCLC. Results from the confirmatory phase III AcceleRET Lung study (NCT04222972) of pralsetinib versus standard of care in the first-line setting are pending.
The role of CYP1A1/2 in cholesterol ester accumulation provides a new perspective for the treatment of hypercholesterolemia
Authors: Jian Lu, Xuyang Shang, Bingyi Yao, Dongyi Sun, Jie Liu, Yuanjin Zhang, He Wang, Jingru Shi, Huaqing Chen, Tieliu Shi, Mingyao Liu, Xin Wang
Journal: Acta Pharmaceutica Sinica B (2022)

Cholesterol is an important precursor of many endogenous molecules. Disruption of cholesterol homeostasis can cause many pathological changes, leading to liver and cardiovascular diseases. CYP1A is widely involved in cholesterol metabolic network, but its exact function has not been fully elucidated. Here, we aim to explore how CYP1A regulates cholesterol homeostasis. Our data showed that CYP1A1/2 knockout (KO) rats presented cholesterol deposition in blood and liver. The serum levels of low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and total cholesterol were significantly increased in KO rats. Further studies found that the lipogenesis pathway (LXRα–SREBP1–SCD1) of KO rats was activated, and the key protein of cholesterol ester hydrolysis (CES1) was inhibited. Importantly, lansoprazole can significantly alleviate rat hepatic lipid deposition in hypercholesterolemia models by inducing CYP1A. Our findings reveal the role of CYP1A as a potential regulator of cholesterol homeostasis and provide a new perspective for the treatment of hypercholesterolemia.
Before-after study with 24-hour ambulatory blood pressure monitoring after the first dose of 5 mg oral minoxidil
Authors: Juan Jimenez-Cauhe, David Saceda-Corralo, Angela Hermosa-Gelbard, Oscar M. Moreno-Arrones, Cristina Pindado-Ortega, Emilio de Dios Berna-Rico, Daniel Ortega-Quijano, Diego Fernandez-Nieto, Sergio Vaño-Galvan
Journal: Journal of the American Academy of Dermatology (2022)
Broad-acting therapeutic effects of miR-29b-chitosan on hypertension and diabetic complications
Authors: David M. Jensen, Peng Han, Lingegowda S. Mangala, Gabriel Lopez-Berestein, Anil K. Sood, Jing Liu, Alison J. Kriegel, Kristie Usa, Michael E. Widlansky, Mingyu Liang
Journal: Molecular Therapy (2022)

MicroRNA miR-29 promotes endothelial function in human arterioles in part by targeting LYPLA1 and increasing nitric oxide production. In addition, miR-29 is a master inhibitor of extracellular matrix gene expression, which may attenuate fibrosis but could also weaken tissue structure. The goal of this study was to test whether miR-29 could be developed as an effective, broad-acting, and safe therapeutic. Substantial accumulation of miR-29b and effective knockdown of Lypla1 in several mouse tissues were achieved using a chitosan-packaged, chemically modified miR-29b mimic (miR-29b-CH-NP) injected systemically at 200 μg/kg body weight. miR-29b-CH-NP, injected once every 3 days, significantly attenuated angiotensin II-induced hypertension. In db/db mice, miR-29b-CH-NP treatment for 12 weeks decreased cardiac and renal fibrosis and urinary albuminuria. In uninephrectomized db/db mice, miR-29b-CH-NP treatment for 20 weeks significantly improved myocardial performance index and attenuated proteinuria. miR-29b-CH-NP did not worsen abdominal aortic aneurysm in ApoE knockout mice treated with angiotensin II. miR-29b-CH-NP caused aortic root fibrotic cap thinning in ApoE knockout mice fed a high-cholesterol and high-fat diet but did not worsen the necrotic zone or mortality. In conclusion, systemic delivery of low-dose miR-29b-CH-NP is an effective therapeutic for several forms of cardiovascular and renal disease in mice. MicroRNA miR-29 promotes endothelial function in human arterioles in part by targeting LYPLA1 and increasing nitric oxide production. In addition, miR-29 is a master inhibitor of extracellular matrix gene expression, which may attenuate fibrosis but could also weaken tissue structure. The goal of this study was to test whether miR-29 could be developed as an effective, broad-acting, and safe therapeutic. Substantial accumulation of miR-29b and effective knockdown of Lypla1 in several mouse tissues were achieved using a chitosan-packaged, chemically modified miR-29b mimic (miR-29b-CH-NP) injected systemically at 200 μg/kg body weight. miR-29b-CH-NP, injected once every 3 days, significantly attenuated angiotensin II-induced hypertension. In db/db mice, miR-29b-CH-NP treatment for 12 weeks decreased cardiac and renal fibrosis and urinary albuminuria. In uninephrectomized db/db mice, miR-29b-CH-NP treatment for 20 weeks significantly improved myocardial performance index and attenuated proteinuria. miR-29b-CH-NP did not worsen abdominal aortic aneurysm in ApoE knockout mice treated with angiotensin II. miR-29b-CH-NP caused aortic root fibrotic cap thinning in ApoE knockout mice fed a high-cholesterol and high-fat diet but did not worsen the necrotic zone or mortality. In conclusion, systemic delivery of low-dose miR-29b-CH-NP is an effective therapeutic for several forms of cardiovascular and renal disease in mice.
Targeting N7-methylguanosine tRNA modification blocks hepatocellular carcinoma metastasis after insufficient radiofrequency ablation
Authors: Shenghua Zhu, Yifan Wu, Xinyue Zhang, Sui Peng, Han Xiao, Shuling Chen, Lixia Xu, Tianhong Su, Ming Kuang
Journal: Molecular Therapy (2022)

Radiofrequency heat ablation is an ideal radical treatment for hepatocellular carcinoma (HCC). However, insufficient radiofrequency ablation (IRFA) could lead to high recurrence of HCC. N
DDX5 mRNA-targeting antisense oligonucleotide as a new promising therapeutic in combating castration-resistant prostate cancer
Authors: Thi Khanh Le, Chaïma Cherif, Kenneth Omabe, Clément Paris, François Lannes, Stéphane Audebert, Emilie Baudelet, Mourad Hamimed, Dominique Barbolosi, Pascal Finetti, Cyrille Bastide, Ladan Fazli, Martin Gleave, François Bertucci, David Taïeb, Palma Rocchi
Journal: Molecular Therapy (2022)

The heat shock protein 27 (Hsp27) has emerged as a principal factor of the castration-resistant prostate cancer (CRPC) progression. Also, an antisense oligonucleotide (ASO) against Hsp27 (OGX-427 or apatorsen) has been assessed in different clinical trials. Here, we illustrate that Hsp27 highly regulates the expression of the human DEAD-box protein 5 (DDX5), and we define DDX5 as a novel therapeutic target for CRPC treatment. DDX5 overexpression is strongly correlated with aggressive tumor features, notably with CRPC. DDX5 downregulation using a specific ASO-based inhibitor that acts on DDX5 mRNAs inhibits cell proliferation in preclinical models, and it particularly restores the treatment sensitivity of CRPC. Interestingly, through the identification and analysis of DDX5 protein interaction networks, we have identified some specific functions of DDX5 in CRPC that could contribute actively to tumor progression and therapeutic resistance. We first present the interactions of DDX5 and the Ku70/80 heterodimer and the transcription factor IIH, thereby uncovering DDX5 roles in different DNA repair pathways. Collectively, our study highlights critical functions of DDX5 contributing to CRPC progression and provides preclinical proof of concept that a combination of ASO-directed DDX5 inhibition with a DNA damage-inducing therapy can serve as a highly potential novel strategy to treat CRPC.